The present invention relates to substituted diphenyl derivatives containing at least (i) a dialkyltriazenyl group, (ii) at least one sulfooxy group and/or at least one sulfamoyloxy group per molecule, their salts, solvates and the solvates of these salts. The invention further relates to a process for preparing these compounds and to their use as medicaments.
For the purposes of the present invention, diphenyl derivatives are phenyl rings joined by a single bond or by a bridge.
Triazene-substituted diphenyl derivatives are known. Thus, DE 17 93 115 A1, DE 21 47 781 A1 and WO 2004/106358 A1 disclose, inter alia, diphenyl derivatives which are substituted by triazene groups and, for example, sulfonic acid or oxycarboxylic acid groups.
Triazene derivatives have in past decades been comprehensively examined for their cytostatic effectiveness. These conventional triazene cytostatics belong to the group of alkylating compounds and, owing to their severe side effects and toxicity, have never found wide clinical use. An exception is dacarbazine (DTIC) which is a prodrug of monomethyl-triazenoimidazolecarboxamide (MTIC) and is used mainly for combating Hodgkin's lymphoma and soft tissue sarcomas (Cancer Treatment Reports 60, 205-211 (1976)). Owing to the light sensitivity of dacarbazine and in particular its side effects, among which leucopenia and thrombopenia are particularly important, a large number of arylalkyltriazenes have been studied with the aim of synthesizing more potent and better tolerable triazenes (Cancer Treatment Reports 60: 125-134 (1976); J. Med. Chem. 23, 1052-1024 (1980)). Despite these efforts, dacarbazine and temozolomide are to date the only triazenes remaining in clinical use of the treatment of glioblastomas, even though they are associated with considerable side effects such as bone marrow depression, neurotoxicity and liver toxicity, emesis, hair loss and exanthems.
A first attempt to overcome the tolerability problems of selected triazenes with a view to selective use in the case of breast cancer is described in DE 17 93 115 A1 and DE 21 47 781 A1.
A second attempt to overcome severe side effects of selected triazenes is described in WO 2004/106358 A1. Some severe side effects of the known triazenes are said to be reduced by introduction of oxycarboxylic acid groups. However, owing to undesirable side effects on the kidney they are not suitable for long-term use.